Synergistic drug effects on growth/survival of neoplastic mast cells. (A) HMC-1.2 cells were incubated in control medium (Co) or in medium containing drugs at 37°C for 48 hours. After incubation with PKC412 (■), bortezomib (●), or drug combinations (▴), cells were analyzed for 3H-thymidine uptake. Results show 3H-thymidine uptake as percentage of control (100%) and represent the mean ± SD of triplicates. (B) Using CalcuSyn software, analyses of dose-effect relationships of PKC412 and bortezomib in HMC-1.2 cells were calculated according to the median effect method of Chou and Talalay.48 A combination index (CI) less than 1 indicates synergism. (C-D) HMC-1.1 cells (C) and HMC-1.2 cells (D) were incubated with increasing concentrations of obatoclax or control medium (Co) for 48 hours. Thereafter, 3H-thymidine uptake was determined. Results are expressed as percentage of control (Co) and represent the mean ± SD of 3 independent experiments. (E-F) HMC-1.1 cells (E) and HMC-1.2 cells (F) were incubated with suboptimal concentrations of obatoclax (1μM) and PKC412 (200nM) alone or in combination at 37°C for 24 hours. Then, the numbers (percentage) of apoptotic cells were determined. Results represent the mean ± SD of 3 independent experiments. As assessed by the CalcuSyn program all drug combination effects were found to be synergistic in nature.
